Helping transplant patients breathe easier

Every minute of every day, lungs provide oxygen needed for survival, and they often do so elegantly unnoticed. Hundreds of millions of tiny air sacs fill and empty tens of thousands of times per day in a healthy pair of lungs. Despite working around the clock, lungs are delicate. If the entire surface area of adult lungs was spread out, it would cover a tennis court, and all of that area is routinely exposed to the environment. When you consider that the only other organ that shares that exposure level is the relatively hardy skin, it's understandable why lungs are especially sensitive to change.

Cancer can take a harsh toll on lungs, which are highly susceptible to things like infections, chemotherapy and radiation. So during a transplant process, the respiratory system can be severely affected.

Dr. Jason Chien is working to lessen the impact on transplant patients. "We're finding that lung function is extremely important in our population. Bad lung function at the beginning of a transplant puts patients at higher risks for worse lung function or death after transplant," Chien said.

Chien is an attending physician at the Seattle Cancer Care Alliance and the medical director of the SCCA's Pulmonary Function Lab. He is also a researcher at the Hutchinson Center. Currently, his research is focused on trying to develop methods that would enable early diagnosis of a complication called bronchiolitis obliterans.

Patients diagnosed too late don't respond to therapy well, and lung complications are not reversible, but Chien is working to halt those complications at an early stage of development. "What we're trying to do is move the window of diagnosis up so that we can implement effective therapy earlier. What we do know is that with the appropriate therapy, the process can be stopped, but not reversed. So the earlier we stop it, the better lung function will be after transplant," Chien said.

Chien is taking several approaches to understanding risks. He advocates evaluating lung function more frequently and earlier, and he has made those recommendations to the National Institutes of Health. He is also devoting part of his work to identifying genetic risk factors. "Are there mutations in a patient's genes or the donor's genes that might influence the risk of developing this sort of complication? And if we can identify these mutations, then we would essentially have a genetic test that we can use to find out if someone is at high risk or low risk for this problem. It will also give us more insight into the biologic mechanisms, leading us to more research down the path toward identifying more effective treatment options."

Because genetic testing is still some time in the future, Chien is focusing on pulmonary function tests for now. "These are tests that all patients have in the transplant process. We evaluate the health of their lungs with this testing. Much of my work has focused on the epidemiology of changes in lung function from pre-transplant all the way to after transplant and long-term survivors," Chien said.

He is looking at two factors — airways and how well lungs absorb gases — as indicators of health. "Every step of the way, if you follow it closely, you can detect changes, that although small, might still be predictive of what could emerge later on. We're looking at both airways and gas absorption as potential indicators," Chien said.

Lung function can also be a good indicator of health of the whole body because lung function is affected by many different organ systems. So lung function tests also measure things like blood vessels, heart and muscles, because those systems are critical to breathing. "Lung function becomes a surrogate measure of overall health," Chien said. "When the overall pulmonary system is compromised, it's a very accurate indicator of how healthy the body is. It gives us a really good measurement of our overall physiology."

In 2011, Dr. Chien left the Hutchinson Center to become director of research at the Seattle offices of Gilead Sciences, a pharmaceutical company.